Impairment of Anti-Aggregatory Responses to Nitric Oxide and Prostacyclin: Mechanisms and Clinical Implications in Cardiovascular Disease

Chirkov, Yuliy Y.; Nguyen, Thanh Ha; Horowitz, John D.

doi:10.3390/ijms23031042

Cited by 19 publications

(12 citation statements)

References 152 publications

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“…Moreover, the level of ET-1 was significantly declined to 313.98 ± 58.09 ng/L ( Figure 8 b, p < 0.01). The increased eNOs had potential to promote the generation of nitric oxide (NO) and then upregulate cGMP protein kinase G (PKG) signaling, thereby inhibiting platelet aggregation [ 31 ].…”

Section: Resultsmentioning

confidence: 99%

A Novel Polysaccharide from AuriculariaAuricula Alleviates Thrombosis Induced by Carrageenan in Mice

Bian

Ji²,

et al. 2022

Molecules

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The increasing incidence of cardiovascular diseases has created an urgent need for safe and effective antithrombotic agents. In this study, we aimed to elucidate the structural characteristics and antithrombotic activity of a novel polysaccharide isolated from Auriculariaauricula fruiting bodies. The purified polysaccharide AAP-b2 (12.02 kDa) was composed of mannose, glucuronic acid, glucose and xylose, with a molar ratio of 89.25:30.50:4.25:1.00. Methylation and NMR analyses showed that AAP-b2 primarily consisted of →2,3)-Manp-(1→, →3)-Manp-(1→, →4)-GlcAp-(1→ and Manp-(1→. A thrombus mouse model induced by carrageenan was used in this research to evaluate its antithrombotic effect. AAP-b2 significantly inhibited platelet aggregation, reduced the black tail length and prolonged the coagulation time, including activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT), exerting a good inhibitory effect on thrombosis in mice. The antithrombotic activity of AAP-b2 was found to be related to the inhibition of platelet activation by regulation of endothelial nitric oxide synthases (eNOs), endothelin-1 (ET-1), prostacyclin (PGI2) and thromboxane B2 (TXB2), along with the enhancement of anticoagulant activity by affecting antithrombin III (AT-III) and protein C (PC) pathways.

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Section: Resultsmentioning

confidence: 99%

A Novel Polysaccharide from AuriculariaAuricula Alleviates Thrombosis Induced by Carrageenan in Mice

Bian

Ji²,

et al. 2022

Molecules

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“…Furthermore, consistent with previous observations in patients with severe angina pectoris, Px normalizes anti-aggregatory responses to the NO donor SNP, and thus ameliorates “NO resistance”, a condition known to be an independent negative prognostic marker [ 5 , 6 ]. This is an important finding, especially in patients with diabetes, as they are at increased risk of adverse outcomes in the presence of acute myocardial ischaemia or heart failure [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Perhexiline Therapy in Patients with Type 2 Diabetes: Incremental Insulin Resistance despite Potentiation of Nitric Oxide Signaling

et al. 2022

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Perhexiline (Px) inhibits carnitine palmitoyltransferase 1 (CPT1), which controls uptake of long chain fatty acids into mitochondria. However, occasional cases of hypoglycaemia have been reported in Px-treated patients, raising the possibility that Px may also increase sensitivity to insulin. Furthermore, Px increases anti-aggregatory responses to nitric oxide (NO), an effect which may theoretically parallel insulin sensitization. We therefore sought to examine these relationships in patients with stable Type 2 diabetes (T2D) and cardiovascular disease (n = 30). Px was initiated, and dosage was titrated, to reach the therapeutic range and thus prevent toxicity. Investigations were performed before and after 2 weeks, to examine changes in insulin sensitivity and, utilizing aggregometry in whole blood, platelet responsiveness to the anti-aggregatory effects of the NO donor sodium nitroprusside (SNP). Other parameters that affect may affect NO signalling were also evaluated. Px substantially potentiated inhibition of platelet aggregation by SNP (from 16.7 ± 3.0 to 27.3 ± 3.7%; p = 0.005). Px did not change fasting blood glucose concentrations but reduced insulin sensitivity (HOMA-IR score increased from median of 4.47 to 6.08; p = 0.028), and increased fasting plasma insulin concentrations (median 16.5 to 19.0 mU/L; p = 0.014). Increases in SNP responses tended (r = −0.30; p = 0.11) to be reciprocally related to increases in HOMA-IR, and increases in HOMA-IR were greater (p = 0.002) in patients without NO-sensitizing effects. No patient developed symptomatic hypoglycaemia, nor was there any other short-term toxicity of Px. Thus, in patients with stable T2D and cardiovascular disease, Px increases anti-aggregatory responsiveness to NO, but is not an insulin sensitizer, and does not induce hypoglycaemia. Absence of NO-sensitizing effect occurs in approximately 30% of Px-treated patients with T2D, and is associated with induction of insulin resistance in these patients.

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“…Inhibited endothelial cell intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) levels increase the stickiness [ 178 ]. These reduce nitric oxide (NO) levels, which support the development of the atherosclerotic plaque [ 179 ]. Furthermore, route (C) and (D) depict the link between mitochondrial dysfunction leading to infections and generating the cytokine storm that leads to plaque disturbance, which is a substantial joint risk factor for PD and cardiovascular disease [ 180 , 181 ].…”

Section: The Relationship Between Parkinson’s Disease Heart Brain And...mentioning

confidence: 99%

Deep Learning Paradigm for Cardiovascular Disease/Stroke Risk Stratification in Parkinson’s Disease Affected by COVID-19: A Narrative Review

Suri¹,

Maindarkar

Sauseng

et al. 2022

Diagnostics

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Background and Motivation: Parkinson’s disease (PD) is one of the most serious, non-curable, and expensive to treat. Recently, machine learning (ML) has shown to be able to predict cardiovascular/stroke risk in PD patients. The presence of COVID-19 causes the ML systems to become severely non-linear and poses challenges in cardiovascular/stroke risk stratification. Further, due to comorbidity, sample size constraints, and poor scientific and clinical validation techniques, there have been no well-explained ML paradigms. Deep neural networks are powerful learning machines that generalize non-linear conditions. This study presents a novel investigation of deep learning (DL) solutions for CVD/stroke risk prediction in PD patients affected by the COVID-19 framework. Method: The PRISMA search strategy was used for the selection of 292 studies closely associated with the effect of PD on CVD risk in the COVID-19 framework. We study the hypothesis that PD in the presence of COVID-19 can cause more harm to the heart and brain than in non-COVID-19 conditions. COVID-19 lung damage severity can be used as a covariate during DL training model designs. We, therefore, propose a DL model for the estimation of, (i) COVID-19 lesions in computed tomography (CT) scans and (ii) combining the covariates of PD, COVID-19 lesions, office and laboratory arterial atherosclerotic image-based biomarkers, and medicine usage for the PD patients for the design of DL point-based models for CVD/stroke risk stratification. Results: We validated the feasibility of CVD/stroke risk stratification in PD patients in the presence of a COVID-19 environment and this was also verified. DL architectures like long short-term memory (LSTM), and recurrent neural network (RNN) were studied for CVD/stroke risk stratification showing powerful designs. Lastly, we examined the artificial intelligence bias and provided recommendations for early detection of CVD/stroke in PD patients in the presence of COVID-19.Conclusion: The DL is a very powerful tool for predicting CVD/stroke risk in PD patients affected by COVID-19.

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Impairment of Anti-Aggregatory Responses to Nitric Oxide and Prostacyclin: Mechanisms and Clinical Implications in Cardiovascular Disease

Cited by 19 publications

References 152 publications

A Novel Polysaccharide from AuriculariaAuricula Alleviates Thrombosis Induced by Carrageenan in Mice

A Novel Polysaccharide from AuriculariaAuricula Alleviates Thrombosis Induced by Carrageenan in Mice

Perhexiline Therapy in Patients with Type 2 Diabetes: Incremental Insulin Resistance despite Potentiation of Nitric Oxide Signaling

Deep Learning Paradigm for Cardiovascular Disease/Stroke Risk Stratification in Parkinson’s Disease Affected by COVID-19: A Narrative Review

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